Cystic fibrosis is the most common fatal hereditary, single gene disease in North America and Europe. The average age of patients with cystic fibrosis at the time of their death is currently about 36 years old. Most of the morbidity and almost all of the mortality is associated with respiratory lung disease characterized by obstruction of the bronchial tubes by abundant thick infected mucus.
The basic defect in cystic fibrosis is a deficiency in the function of the protein known as the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel allowing the passage of salt, bicarbonate and other negatively charged substances across the apical membranes of epithelial cells in the airways, pancreas, liver, intestinal tract and reproductive system. The absence of CFTR in cystic fibrosis epithelia leads to a marked decrease of water and salt secretion which results in a characteristic increase in the viscosity of secretions. These secretions bind to the walls of the bronchial tubes and form tenacious plaques that cannot be carried up to the throat by cilia that line the airways. Subsequently, inhaled bacteria become trapped in these secretions (or mucus), proliferate and initiate a cycle of events including airway tissue destruction, airway inflammation and the accumulation of even greater amounts of thick, adherent mucus. All of these events, which eventually lead to respiratory insufficiency and death, are initiated by the lung's inability in the absence of CFTR to clear the viscous mucus from the airways. Correction of this basic defect in airway clearance is the goal of many therapeutic developments aiming to control or cure cystic fibrosis.
While defective mucociliary clearance is most obvious in patients with cystic fibrosis, many more patients suffering from common respiratory ailments such as chronic bronchitis, bronchiectasis, asthma, muscular dystrophy, neuromuscular degenerative disorders, post-operative atelectasis and thoracic wall defects are also afflicted by their incapacity to adequately clear their airways of abundant mucus. Consequently, these patients are at high risk of presenting multiple lung infections. They require frequent use of antibiotics and medical services, as well as repeated hospitalizations. Improved clearance of thick respiratory secretions in all of these medical conditions is a fundamental objective of current therapeutic approaches.
The cornerstone of therapy for cystic fibrosis and other respiratory ailments involving inspissated mucus is chest physiotherapy aimed at moving the bronchial secretions up towards the throat. Several respiratory physiotherapy approaches have been developed to address the problem of therapeutic airway clearance. The best known technique of airway clearance against which other methods are compared remains postural drainage with clapping. This technique necessarily requires a therapist, often a family member, who repeatedly claps the chest wall of the patient with an open hand while the patient is positioned in such a way that the bronchial tube being drained is inclined at an angle favoring movement of mucus down a slope. The patient's position is changed periodically to allow all major bronchial tubes to be treated. Because the technique requires the help of a therapist and because the positions and clapping are uncomfortable procedures, patients most often abandon such potentially important therapy during adolescence.
Since airway clearance is such an important part of the management of respiratory diseases with thick mucus, several alternative techniques have been developed to improve compliance. Among these techniques are the following:
Autogenic drainage is a technique in which a superficial breathing pattern at low lung volumes is followed by huffing or forced expiratory bursts to move the mucus towards the throat and provoke a cough with expectoration.
PEP mask is a technique in which a positive expiratory pressure is applied to the mouth with a mask during exhalation in an attempt to maintain the bronchial tubes open as the air is exiting the lungs. This allows mucus to be displaced more effectively than with simple cough.
Flutter is a simple device into which patients blow slowly and which creates a positive expiratory pressure much like the PEP mask. However, in addition, the Flutter creates a mild vibration at the mouth allowing adherent mucus to more readily be dislodged from the bronchial tubes.
The mechanical percussor is an electrical device based along the same principles as postural drainage with clapping, but the major advantage is that the patient can perform the treatments alone without the need of a therapist. However, the technique is awkward since certain areas of the chest are more difficult to reach. Additionally, the technique is uncomfortable since the percussion is repeated over a diseased chest.
The pneumatic vest is an inflatable vest connected to a pneumatic compressor allowing repeated mechanical compressions of the thorax at high frequencies.
Very little data exists comparing the effectiveness of these airway clearance techniques to postural drainage with clapping, and none have proven to be more effective. The most significant advantage of these alternative chest physiotherapy techniques is the autonomy it gives to patients since they do not require a therapist. However, it has been found that the majority of patients use these techniques only sporadically, and sometimes stop them altogether, since they are unable to mobilize significant amounts of mucus and do not feel any benefits.
A real need, therefore, exists for improved airway clearance techniques that will be effective and favor patient compliance. Accordingly, it is an object of the present application to obviate or mitigate some or all of the above disadvantages.